Dental caries continue to be a major disease in the world today with growth due to increasing world population and greater availability of disposable income in developing countries allowing for greater purchases of sweets. Even in the United States, there is a problem of some 80% of the caries in 20% of the population and the disease become lifelong now that older Americans are retaining their teeth while at the same time having reduced salivary flow become of the medicines they take. Moreover, there are indications locally that caries in children is increasing, albeit slowly. Overall, caries appears not to be under control, even in industrialized countries. The best control strategies for caries involve reducing the virulence of the pathogens. For organisms such as mutans streptococci, control can depend on inhibition of oral attachment, mainly to plaque, or reductions in acid tolerance. Since caries occurs mainly at low pH values, virulence is closely related to acid tolerance, which appears to be set mainly by F(H+)-ATPases, specifically by amounts of the enzyme per cell and pH-activity profiles of the enzymes of particular bacteria. This application is focused on acid tolerance and F-ATPases. It proposes continuation of ongoing research but also addresses new views of the multi-organism etiology of caries, of fatty- acid modulation of membrane enzymes and of substrate limitation of F- ATPase activities. The specific aims are: 1. Further studies of the F- ATPases of oral bacteria with orientation to defining the molecular bases for differences in acid tolerance among the enzymes of organisms with high and low tolerance and to evaluation of physiological controlling factors for the F-ATPase activities of the organisms, including ATP supply and associations with membrane lipids. Modulation of transmembrane transport systems by membrane fatty acids will be investigated also; 2. Studies of the acid-base physiology of acid-tolerant strains of oral streptococci selected from plaque through growth in acidified media. The work will include studies of the F-ATPase of the organisms, buffer capacities of cells to the organisms compared with mutans streptococci, responses to fluoride and other weak acids, capacities to develop acid-adaptive response, and other factors that may allow for glycolytic acid production at low pH values.